AUTHOR=Xie Hui , Yuan Ce , Li Jin-jiang , Li Zhao-yang , Lu Wei-cheng 

TITLE=Potential Molecular Mechanism of TNF Superfamily-Related Genes in Glioblastoma Multiforme Based on Transcriptome and Epigenome

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.576382

DOI=10.3389/fneur.2021.576382

ISSN=1664-2295

ABSTRACT=Objective: This study aimed to investigate the molecular mechanism of tumor necrosis factor (TNF) superfamily-related genes and potential therapeutic drugs for glioblastoma multiforme (GBM) patients based on transcriptome and epigenome.
Methods: Gene expression data, corresponding clinical data and methylation data of GBM samples and normal samples in TCGA-GBM and GTEx dataset were downloaded. The TNF-related genes were obtained respectively from two groups in TCGA dataset. Then, the TNF-related differentially expressed genes (DEGs) were investigated between two groups, followed by enrichment analysis. Moreover, TNF superfamily-related genes expression and upstream methylation regulation was investigated to explore candidate genes and prognostic model. Finally, the protein expression level of candidate genes was performed, followed by drug prediction analysis. 
Results: A total of 41 DEGs including 4 ligands, 18 receptors and 19 downstream signaling molecules were revealed between two groups. These DEGs were mainly enriched in pathway like TNF signaling and functions like response to TNF. A total of 5 methylation site regulated prognosis-related genes including TNF Receptor Superfamily Member (TNFRSF) 12A, TNFRSF11B and CD40 were explored. The prognosis model constructed by 5 genes showed a well prediction effect on current dataset and verification dataset. Finally, drug prediction analysis showed that zoledronic acid (ZA)-TNFRSF11B was the unique drug-gene relation in both two databases.
Conclusion: Methylation-driven gene TNFRSF12A might participate in the development of GBM via response to TNF biological process and TNF signaling pathway, and significantly associated with prognosis. ZA that targeting TNFRSF11B expression might be potential effective drug for clinical treatment of GBM.